Small changes in core temperature have been shown to trigger a significant adrenergic response which may be the etiology of cold- induced myocardial ischemia. However, previous studies investigating this adrenergic response have been performed in young individuals, and the effects of age are unknown. In addition, no studies have been performed in humans to assess methods to block the potentially harmful effects of hypothermia. We designed a study to compare the adrenergic response to hypothermia in young vs. old human volunteers, and the use of alpha-adrenoceptor antagonists to block this response. The study was completed in June of 1996, The data show that the elderly are less able to maintain body temperature during cold challenge. This is due to a desensitization of the alpha receptor and the inability to vasocontrict in the presence of normal or even increased norepinephrine release. Shivering and total body oxygen consumption were also impaired in the elderly as demonstrated by reduced gain of this response. The elderly are more sensitive to the thermoregulatory effects of alpha blockade compared to the young. Alpha-antagonists selectively impair the vasoconstriction response to core hypothermia, but not the shivering response. This selective inhibition could be clinically useful since the adverse cardiovascular effects of hypothermia appear to be adrenergically mediated.